This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to Kv potassium channel family, hereinafter referred to as hKv4.3. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides.
The transient outward potassium channel (Ito) is a member of the potassium channel Kv family and is one of the major ionic current involved in the repolarization of the cardiac atrial action potential. In the ventricle, it is reponsible for the early repolarization of the action potential. Its electrophysiological characteristics have been demonstrated in human cardiac cell and it is suggested that alterations of its activation and inactivation kinetics play a major role in the genesis of re-entry.
The gene coding for the human channel responsible for this current is still not identified. Amongst the different candidates, it appears that Kv4.3 may be responsible for Ito in the dog and the rat (Circ Res, 1996, 79; 659-668). More recently, a partial fragment of a rat Kv4.3 isoform has been identified (Takimoto et al, Circ Res, 1997, 81:533-539; Ohya S et al, FEBS Letters, 1997,420: 47-53). This comprised an insertion of an extra 19 amino acids. In human heart, the gene coding for Ito has not yet been identified. There remains a need for identification and characterization of further members of the Kv potassium channel family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, cardiac arrhythmias and Alzheimer""s disease.
In one aspect, the invention relates to hKv4.3 polypeptides and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such hKv4.3 polypeptides and polynucleotides. Such uses include the treatment of cardiac arrhythmias and Alzheimer""s disease, among others. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with hKv4.3 imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate hKv4.3 activity or levels.